Piloting the zebrafish genome browser.

This correspondence is a primer for the zebrafish research community on zebrafish tracks available in the UCSC Genome Browser at http://genome.ucsc.edu based on Sanger's Zv4 assembly. A primary capability of this facility is comparative informatics between humans (as well as many other model organisms) and zebrafish. The zebrafish genome sequencing project has played important roles in mutant mapping and cloning, and comparative genomic research projects. This easy-to-use genome browser aims to display and download useful genome sequence information for zebrafish mutant mapping and cloning projects. Its user-friendly interface expedites annotation of the zebrafish genome sequence.     

The Ensembl Web site: mechanics of a genome browser

The Ensembl Web site (http://www.ensembl.org/) is the principal user interface to the data of the Ensembl project, and currently serves >500,000 pages (approximately 2.5 million hits) per week, providing access to >80 GB (gigabyte) of data to users in more than 80 countries. Built atop an open-source platform comprising Apache/mod_perl and the MySQL relational database management system, it is modular, extensible, and freely available. It is being actively reused and extended in several different projects, and has been downloaded and installed in companies and academic institutions worldwide. Here, we describe some of the technical features of the site, with particular reference to its dynamic configuration that enables it to handle disparate data from multiple species.     

The generic genome browser: a building block for a model organism system database

The Generic Model Organism System Database Project (GMOD) seeks to develop reusable software components for model organism system databases. In this paper we describe the Generic Genome Browser (GBrowse), a Web-based application for displaying genomic annotations and other features. For the end user, features of the browser include the ability to scroll and zoom through arbitrary regions of a genome, to enter a region of the genome by searching for a landmark or performing a full text search of all features, and the ability to enable and disable tracks and change their relative order and appearance. The user can upload private annotations to view them in the context of the public ones, and publish those annotations to the community. For the data provider, features of the browser software include reliance on readily available open source components, simple installation, flexible configuration, and easy integration with other components of a model organism system Web site. GBrowse is freely available under an open source license. The software, its documentation, and support are available at http://www.gmod.org.     

Scanning the human genome at kilobase resolution

Normal genome variation and pathogenic genome alteration frequently affect small regions in the genome. Identifying those genomic changes remains a technical challenge. We report here the development of the DGS (Ditag Genome Scanning) technique for high-resolution analysis of genome structure. The basic features of DGS include (1) use of high-frequent restriction enzymes to fractionate the genome into small fragments; (2) collection of two tags from two ends of a given DNA fragment to form a ditag to represent the fragment; (3) application of the 454 sequencing system to reach a comprehensive ditag sequence collection; (4) determination of the genome origin of ditags by mapping to reference ditags from known genome sequences; (5) use of ditag sequences directly as the sense and antisense PCR primers to amplify the original DNA fragment. To study the relationship between ditags and genome structure, we performed a computational study by using the human genome reference sequences as a model, and analyzed the ditags experimentally collected from the well-characterized normal human DNA GM15510 and the leukemic human DNA of Kasumi-1 cells. Our studies show that DGS provides a kilobase resolution for studying genome structure with high specificity and high genome coverage. DGS can be applied to validate genome assembly, to compare genome similarity and variation in normal populations, and to identify genomic abnormality including insertion, inversion, deletion, translocation, and amplification in pathological genomes such as cancer genomes.     

From human genome to cancer genome: The first decade

The realization that cancer progression required the participation of cellular genes provided one of several key rationales, in 1986, for embarking on the human genome project. Only with a reference genome sequence could the full spectrum of somatic changes leading to cancer be understood. Since its completion in 2003, the human reference genome sequence has fulfilled its promise as a foundational tool to illuminate the pathogenesis of cancer. Herein, we review the key historical milestones in cancer genomics since the completion of the genome, and some of the novel discoveries that are shaping our current understanding of cancer.     

Gene amplifications at chromosome 7 of the human gastric cancer genome

Genetic aberrations at chromosome 7 are known to be related with diverse human diseases, including cancer and autism. In a number of cancer research areas involving gastric cancer, several comparative genomic hybridization studies employing metaphase chromosome or BAC clone microarrays have repeatedly identified human chromosome 7 as containing 'regions of changes' related with cancer progression. cDNA microarray-based comparative genomic hybridization can be used to directly identify individual target genes undergoing copy number variations. Copy number change analysis for 17,000 genes on a microarray format was performed with tumor and normal gastric tissues from 30 patients. A group of 90 genes undergoing copy number increases (gene amplification) at the p11 approximately p22 or q21 approximately q36 region of chromosome 7 is reported. The list of genes includes wingless-type MMTV integration site family member 2 (WNT2), a proto-oncogene and acyloxyacyl hydrolase (AOAH) that was amplified in >80% of the tested cases. The amplified genes are those functioning in the biological processes such as signal transduction pathways, cell proliferation, metabolism, transport, inflammatory response and protein folding or proteolysis. Also found in the list are genes that are targets for drug development, such as maltase-glucoamylase (MGAM), cyclin-dependent kinase 5 (CDK5), neuropeptide Y (NPY) and dopa decarboxylase (DDC). The current dataset can be used as one of the resources in understanding genetic aberrations of chromosome 7 in human gastric cancer.     

The genome of human coronavirus strain 229E

The genomic RNA of human coronavirus strain 229E (HCV 229E) migrated on polyacrylamide gels as a single peak with a mol. wt. of 5.8 X 10(6). Denaturation of the genome with formaldehyde did not alter its electrophoretic mobility, which suggests that the HCV 229E genome is a single-stranded molecule. At least 30% of the genomic RNA was shown to contain covalently attached polyadenylic acid [poly(A)]sequences by binding the RNA to an oligo(dT)-cellulose column. These poly(A) tracts were shown to be about 70 nucleotides in length by measuring the resistance to digestion of HCV 229E RNA with pancreatic and T1 RNases. Finally, the genomic RNA was shown to terminate at or near the 3'-terminus on the basis of its susceptibility to polynucleotide phosphorylase.     

The challenge of documenting mutation across the genome: the human genome variation society approach

New methods for the detection of mutations and the completion of the human genome sequencing project have contributed to an exponential rise in variation information that must be collected, quality controlled, documented, and stored safely to ensure future availability to health care professionals, researchers, and others. There may be anywhere from one to more than 1,000 mutations in any given gene. To date, this information has been collected by general databases such as Online Mendelian Inheritance in Man (OMIM) or the Human Gene Mutation Database (HGMD), which collect only published mutations and, in the case of OMIM, selected published mutations. Unpublished mutations have made their way into Locus Specific Databases (LSDBs), and these can often contain as many unpublished mutations as published ones, in addition to other more detailed gene-specific information. LSDBs, however, do not exist for all genes at this time. Through their interactions, a number of members of the Human Genome Variation Society (HGVS) have developed nomenclature, standard software to curate mutations in gene specific databases, a WayStation to collect and review new mutations from research and diagnostic laboratories, and central databases to store and display these mutations and their associated phenotypes. Nomenclature is now well defined for the commonest types of mutation, with work continuing on systematically naming the more complex types. Other projects, such as dedicated specialized software for LSDBs, are in the early stages of development.     

Heterogeneous gene distribution reflects human genome complexity as detected at the cytogenetic level

Fragile sites are specific regions of chromosomes prone to breakage when cells are cultured under specific conditions. These sites are divided into two classes: common and rare. Common fragile sites are expressed in all individuals at different frequencies, whereas rare ones are found only in certain individuals. Common and rare fragile sites have been shown to display a number of characteristics of instability being preferential sites for chromosomal deletions, duplications, and rearrangements. Moreover, a majority of mapped oncogenes are located at or near these fragile sites. These observations have led to the suggestion that both classes of fragile sites may play a significant role in chromosomal rearrangements involved in oncogene activation or tumor supressor gene inactivation. For these reasons, involvement of common and rare fragile sites and their relevance to specific chromosome breakpoints in cancer have received much attention. In this study, which reports on the cytogenetic findings obtained from 256 patients with chronic myelocytic leukemia, 103 with acute myelocytic leukemia, 40 with acute lymphocytic leukemia, 33 with myelodysplastic syndrome, we documented the fragile sites involved in chromosomal aberrations involving oncogenes, tumor supressor genes, and other known genes important in cell cycle regulation localized at these sites.     

关于人类基因组计划研究问题

一、从基因到人类基因组计划 自1868年遗传学的奠基人Mendel提出遗传因子的假说以来,人类对遗传物质和遗传规律的研究已走过了130多年的历史.